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Tumor Infiltrating Lymphocytes as a Prognostic and Predictive Biomarker in Breast Cancer

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Molecular Pathology of Breast Cancer

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Abstract

Tumor infiltrating lymphocytes (TILs) have been recognized in various cancers and may reflect a host immune response to malignant cells. TILs are a heterogeneous population of various types of mononuclear cells, including CD8 or CD4 + T cells and their subsets, B cells, myeloid derived suppressor cells (MDSC), macrophages, and other cells. Immunosuppressive factors in the tumor microenvironment (TME) that inhibit recruitment and function of TILs include immunosuppressive cells, cytokines secreted by tumor or mesenchymal cells, and co-inhibitory ligands expressed by tumor cells. Despite this complex interplay of immune cells and the TME, higher TIL density is associated with favorable prognosis in certain breast cancer subtypes, including HER2 overexpressing cancers, and “triple negative” cancers that do not express the estrogen and progesterone receptors or overexpress HER2. TILs infiltrating the tumor stroma (sTILs) are associated with higher rates of complete pathologic response to neoadjuvant chemotherapy, decreased recurrence and improved survival in early stage triple negative and HER2-positive breast cancer treated with adjuvant systemic therapy. An international working group has published guidelines on reporting TILs in pathology specimens. In this chapter we review the composition of TILs, mechanisms of immune evasion, recommendations for TILs measurement, and data supporting use of TILs as a prognostic and predictive biomarker in breast cancer.

Murali Janakiram and Hina Khan are contributed equally to this work.

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Authors and Affiliations

  1. Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, 1695 Eastchester Road, Bronx, NY, 10461, USA

    Murali Janakiram, Hina Khan, Xingxing Zang & Joseph A. Sparano

  2. Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, 1695 Eastchester Road, Bronx, NY, 10461, USA

    Murali Janakiram, Hina Khan, Xingxing Zang & Joseph A. Sparano

  3. Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, 1695 Eastchester Road, Bronx, NY, 10461, USA

    Susan Fineberg

  4. Department of Microbiology and Immunology, Montefiore Medical Center, Albert Einstein College of Medicine, 1695 Eastchester Road, Bronx, NY, 10461, USA

    Murali Janakiram & Xingxing Zang

Authors
  1. Murali Janakiram
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  2. Hina Khan
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  3. Susan Fineberg
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  4. Xingxing Zang
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  5. Joseph A. Sparano
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Correspondence to Joseph A. Sparano .

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Editors and Affiliations

  1. Pathology & Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA

    Sunil Badve

  2. Indiana University School of Medicine, Dept of Pathology & Laboratory Medicine Indiana University School of Medicine, Indianapolis, Indiana, USA

    Yesim Gökmen-Polar

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Janakiram, M., Khan, H., Fineberg, S., Zang, X., Sparano, J.A. (2016). Tumor Infiltrating Lymphocytes as a Prognostic and Predictive Biomarker in Breast Cancer. In: Badve, S., Gökmen-Polar, Y. (eds) Molecular Pathology of Breast Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-41761-5_12

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